Fetal asphyxia is one of the most common forms of fetal stress. Recovery of the fetus from periods of asphyxia depends upon the cardiovascular and endocrine adjustments stimulated by the asphyxia. The experiments proposed in this grant application are designed to investigate the mechanism of the response of the fetal renin-angiotensin system, and hormonal system directly related to the control of fetal blood volume pressure and flow. Specifically, we will investigate the interaction between alterations in arterial oxygen and carbon dioxide tension, and arterial blood pressure in the control of renin secretion and angiotensin II information. In addition, we will investigate the role of fetal carotid and aortic chemoreceptors in the stimulation of renin and angiotensin II during hypoxia and/or hypercapnia. To answer these questions, we will prepare pregnant ewes and their fetal sheep with chronically implanted vascular catheters. We will measure maternal and fetal renin, angiotensin II, and aldosterone responses to ventilatory hypoxia with and without concomitant hypercapnia with and without pharmacologic control of fetal arterial blood pressure. The role of fetal chemoreceptors can be assessed by comparing the response in chemoreceptor-denervated fetuses to responses in intact retuses. The results of these experiments will improve our understanding of the homeostatic fetal responses to stress by determining the mechanisms underlying the fetal stress responses. Only by improving an understanding of fetal responses to asphyxia can it be possible to eventually devise therapeutic strategies to reduce the probability of fetal morbidity and mortality during episodes of asphyxia.